Multinodular goiter is probably a lifelong condition that has its inception in adolescence or at puberty. Minimal diffuse enlargement of the thyroid gland is found in many teenage boys and girls, and is almost a physiologic response to the complex structural and hormonal changes occurring at this time. It usually regresses, but occasionally (much more commonly in girls) it persists and undergoes further growth during pregnancy. This course of events has not been documented as well as might be desired in sporadic nodular goiter, but it is the usual evolution in areas where mild endemic goiter is found.
Patients with multinodular goiter seek medical attention for many reasons. Perhaps most commonly they consult a physician because a lump has been discovered in the neck, or because a growth spurt has been observed in a goiter known to be present for a long time. Sometimes the increase in the size of the goiter will cause pressure symptoms, such as difficulty in swallowing, cough, respiratory distress, or the feeling of a lump in the throat. Rarely, an area of particularly asymmetrical enlargement may impinge upon or stretch the recurrent laryngeal nerve. Commonly the goiter is discovered by a physician in the course of an examination for some other condition. An important scenario is for the patient to seek medical attention because of cardiac irregularities or congestive heart failure, which proves to be the result of slowly developing thyrotoxicosis. (The issue is discussed more fully later in this chapter). Many times the goiter grows gradually for a period of a few too many years, and then becomes stable with little tendency for further growth. It is rare for any noteworthy spontaneous reduction in the size of the thyroid gland to occur, but patients often describe fluctuations in the size of the goiters and the symptoms they give. These are usually subjective occurrences, and more often than not the physician is unable to corroborate the changes that the patient describes. On the other hand, it could be that changes in blood flow through the enlarged gland account for the symptoms.
Occasionally, a sudden increase in the size of the gland is associated with sharp pain and tenderness in one area. This event suggests hemorrhage into a nodular cyst of the goiter, which can be confirmed by ultrasound. Within 3-4 days the symptoms subside, and within 2-3 weeks the gland may revert to its previous dimensions. In such a situation, acute thyrotoxicosis may develop and subside spontaneously53,54 (Figure 17-6).
Figure 6. T4 and T3 levels in a patient with multinodular goiter. Desiccated thyroid was withdrawn because of thyrotoxic symptoms. Note high T3 and T4 peak values in mid 1974 due to acute hemorrhage in thyroid nodule (with permission ref. 53).
Rarely, if ever, do the patients become hypothyroid and if they do, the diagnosis is more probably Hashimoto's thyroiditis than nodular goiter. In a study in clinically euthyroid subjects with multinodular goiter, 13 out of 22 had subnormal TSH release after TRH.12 If the goiter is present for a long time, thyrotoxicosis develops in a large number of patients. In a series collected many years ago at the Mayo Clinic, 60% of patients with MNG over 60 were thyrotoxic.55 The average duration of the goiter before the onset of thyrotoxicosis was 17 years; the longer the goiter had been present, the greater was the tendency for thyrotoxicosis to develop. This condition appears to occur because with the passage of time, autonomous function of the nodules develops. In a more recent study of patients with euthyroid multinodular goiter, thyroid function was autonomous in 64 and normal in 26. After a mean follow-up of 5.0 years (maximum 12 years) 18 patients with autonomous thyroid function became overtly hyperthyroid and in 6 patients with primarily normal thyroid function autonomy developed.56 In Figure 17-7 (below) the typical course of thyroid function tests is illustrated in a patient with multinodular goiter starting from complete euthyroidism on to overt thyrotoxicosis. Occasionally a single discrete nodule in the thyroid gland becomes sufficiently active to cause thyrotoxicosis and to suppress the activity of the rest of the gland (see Chapt.13). If these patients are given thyroid hormone, continued function of nodules can be demonstrated by radioiodine scanning techniques. Thus, these nodules have become independent of pituitary control. When patients with euthyroid multinodular goiter are frequently tested, it appears that in some of them occasional transient increases of serum T3 and/of T4 are seen57 (Figure 17-8, below). The possibility that the abrupt development of hyperthyroidism may follow administration of large amounts of iodine to these patients has already been mentioned.49
Figure 7. Course of thyroid function tests, including the increment of TSH in response to TRH in a patient who demonstrated the whole functional cycle from non-autonomy (1979), through autonomy (1981) up to overt hyperthyroidism (1984) (with permission ref. 56).
Figure 8. Serum T4 and T3 levels during a follow-up of 20 and 27 months in 2 patients ("--" and "--"), both aged 60 years, with euthyroid multinodular goiter. The continuous lines indicate 95 percent confidence limits of the normal range (with permission ref. 57).
Occasionally an invasive thyroid cancer develops in a multinodular goiter. This fact brings the discussion to one of the most serious problems relating to multinodular goiter, that of carcinoma.